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成年雌性B6C3F1小鼠通过长期饮用含乙醇的液体饲料导致免疫抑制。

Immunosuppression in adult female B6C3F1 mice by chronic exposure to ethanol in a liquid diet.

作者信息

Holsapple M P, Eads M, Stevens W D, Wood S C, Kaminski N E, Morris D L, Poklis A, Kaminski E J, Jordan S D

机构信息

Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.

出版信息

Immunopharmacology. 1993 Jul-Aug;26(1):31-51. doi: 10.1016/0162-3109(93)90064-w.

Abstract

The overall objective of these studies was to characterize the effects of ethanol on the immunocompetence of adult female B6C3F1 mice. To obtain a significant suppression in the antibody response to SRBC, splenocytes from untreated mice had to be directly exposed to concentrations of ethanol from 0.3% to 3.0%, or to acetaldehyde at concentrations greater than 0.03%. We do not believe that these results are consistent with a role by a direct effect by either ethanol or its primary metabolite because these concentrations are higher than what could be obtained as reasonable blood levels. For in vivo exposure, we employed a pair-feeding regimen which was based on a liquid diet containing 5% ethanol (v/v) that provided 36% of the caloric intake as ethanol. Our results indicated that there was a definite temporal relationship to the consequent suppression of the antibody response to SRBC in that no effect was observed after 14 days exposure, and that the magnitude of the suppression increased from 18% after 21 days to 70% after 42 days. We also monitored the liver for histopathology and observed that the ethanol-induced liver damage was restricted to steatosis (fatty liver), which was also manifested with time and which was most pronounced after 42 days exposure. In contrast to our results with the in vivo antibody response, we saw no effect on mitogen-induced proliferation by splenocytes from ethanol-treated mice. These results prompted us to measure in vitro antibody responses by splenocytes from ethanol-treated mice. We saw no suppression of the in vitro antibody responses to SRBC, DNP-Ficoll or LPS after any length of exposure to ethanol, and speculated that the basis for the suppression of the in vivo antibody response was an indirect consequence of exposure. We subsequently determined that when normal splenocytes were cultured in 5% serum from ethanol-exposed mice (42-day group), there was a > 80% suppression relative to the serum from the pair-fed controls. As important controls for these studies, we have demonstrated that there was no difference between the responses of normal lymphocytes cultured in 5% normal mouse serum and in 5% serum taken from the pair-fed restricted controls. A determination of the ethanol content in the serum from ethanol-exposed mice (42-day group) indicated that the amount of ethanol present in these cultures was < 0.003%.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

这些研究的总体目标是描述乙醇对成年雌性B6C3F1小鼠免疫能力的影响。为了显著抑制对绵羊红细胞(SRBC)的抗体反应,未处理小鼠的脾细胞必须直接暴露于浓度为0.3%至3.0%的乙醇中,或暴露于浓度大于0.03%的乙醛中。我们认为这些结果与乙醇或其主要代谢产物的直接作用不符,因为这些浓度高于合理的血液水平。对于体内暴露,我们采用了一种配对喂养方案,该方案基于含有5%乙醇(体积/体积)的液体饮食,乙醇提供了36%的热量摄入。我们的结果表明,对SRBC抗体反应的后续抑制存在明确的时间关系,即暴露14天后未观察到影响,抑制程度从21天后的18%增加到42天后的70%。我们还监测了肝脏的组织病理学,观察到乙醇诱导的肝损伤仅限于脂肪变性(脂肪肝),其也随时间表现出来,在暴露42天后最为明显。与我们在体内抗体反应中的结果相反,我们未观察到乙醇处理小鼠的脾细胞对丝裂原诱导的增殖有影响。这些结果促使我们测量乙醇处理小鼠脾细胞的体外抗体反应。在暴露于乙醇的任何时长后,我们均未观察到对SRBC、二硝基苯 - 聚蔗糖(DNP-Ficoll)或脂多糖(LPS)的体外抗体反应受到抑制,并推测体内抗体反应受到抑制的基础是暴露的间接后果。我们随后确定,当正常脾细胞在来自乙醇暴露小鼠(42天组)的5%血清中培养时,相对于配对喂养对照的血清,抑制率>80%。作为这些研究的重要对照,我们已证明在5%正常小鼠血清中培养的正常淋巴细胞与在来自配对喂养受限对照的5%血清中培养的正常淋巴细胞的反应之间没有差异。对乙醇暴露小鼠(42天组)血清中乙醇含量的测定表明,这些培养物中存在的乙醇量<0.003%。(摘要截断于400字)

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